Scene-selectivity in CA1/subicular complex: Multivoxel pattern analysis at 7T.

Prior univariate functional magnetic resonance imaging (fMRI) studies in humans suggest that the anteromedial subicular complex of the hippocampus is a hub for scene-based cognition. However, it is possible that univariate approaches were not sufficiently sensitive to detect scene-related activity in other subfields that have been implicated in spatial processing (e.g., CA1). Further, as connectivity-based functional gradients in the hippocampus do not respect classical subfield boundary definitions, category selectivity may be distributed across anatomical subfields. Region-of-interest approaches, therefore, may limit our ability to observe category selectivity across discrete subfield boundaries. To address these issues, we applied searchlight multivariate pattern analysis to 7T fMRI data of healthy adults who undertook a simultaneous visual odd-one-out discrimination task for scene and non-scene (including face) visual stimuli, hypothesising that scene classification would be possible in multiple hippocampal regions within, but not constrained to, anteromedial subicular complex and CA1. Indeed, we found that the scene-selective searchlight map overlapped not only with anteromedial subicular complex (distal subiculum, pre/para subiculum), but also inferior CA1, alongside posteromedial (including retrosplenial) and parahippocampal cortices. Probabilistic overlap maps revealed gradients of scene category selectivity, with the strongest overlap located in the medial hippocampus, converging with searchlight findings. This was contrasted with gradients of face category selectivity, which had stronger overlap in more lateral hippocampus, supporting ideas of parallel processing streams for these two categories. Our work helps to map the scene, in contrast to, face processing networks within, and connected to, the human hippocampus.

Functional MRI applications for intra-axial brain tumours: uses and nuances in surgical practise.

PURPOSE: Functional MRI (fMRI) has well-established uses to inform risks and plan maximally safe approaches in neurosurgery. In the field of brain tumour surgery, however, fMRI is currently in a state of clinical equipoise due to debate around both its sensitivity and specificity. MATERIALS AND METHODS: In this review, we summarise the role and our experience of fMRI in neurosurgery for gliomas and metastases. We discuss nuances in the conduct and interpretation of fMRI that, based on our practise, most directly impact fMRI's usefulness in the neurosurgical setting. RESULTS: Illustrated examples in which fMRI in our hands directly influences the neurosurgical treatment of brain tumours include evaluating the probability and nature of functional risks, especially for language functions. These presurgical risk assessments, in turn, help to predict the resectability of tumours, select or deselect patients for awake surgery, indicate the need for neurophysiological monitoring and guide the optimal use of intra-operative stimulation mapping. A further emerging application of fMRI is in measuring functional adaptation of functional networks after (partial) surgery, of potential use in the timing of further surgery. CONCLUSIONS: In appropriately selected patients with a clearly defined surgical question, fMRI offers a valuable complementary tool in the pre-surgical evaluation of brain tumours. However, there is a great need for standards in the administration and analysis of fMRI as much as in the techniques that it is commonly evaluated against. Surprisingly little data exists that evaluates the accuracy of fMRI not just against complementary methods, but in terms of its ultimate clinical aim of minimising post-surgical morbidity.

Superior Verbal Memory Outcome After Stereotactic Laser Amygdalohippocampotomy.

Objective: To evaluate declarative memory outcomes in medically refractory epilepsy patients who underwent either a highly selective laser ablation of the amygdalohippocampal complex or a conventional open temporal lobe resection. Methods: Post-operative change scores were examined for verbal memory outcome in epilepsy patients who underwent stereotactic laser amygdalohippocampotomy (SLAH: n = 40) or open resection procedures (n = 40) using both reliable change index (RCI) scores and a 1-SD change metric. Results: Using RCI scores, patients undergoing open resection (12/40, 30.0%) were more likely to decline on verbal memory than those undergoing SLAH (2/40 [5.0%], p = 0.0064, Fisher's exact test). Patients with language dominant procedures were much more likely to experience a significant verbal memory decline following open resection (9/19 [47.4%]) compared to laser ablation (2/19 [10.5%], p = 0.0293, Fisher's exact test). 1 SD verbal memory decline frequently occurred in the open resection sample of language dominant temporal lobe patients with mesial temporal sclerosis (8/10 [80.0%]), although it rarely occurred in such patients after SLAH (2/14, 14.3%) (p = 0.0027, Fisher's exact test). Memory improvement occurred significantly more frequently following SLAH than after open resection. Interpretation: These findings suggest that while verbal memory function can decline after laser ablation of the amygdalohippocampal complex, it is better preserved when compared to open temporal lobe resection. Our findings also highlight that the dominant hippocampus is not uniquely responsible for verbal memory. While this is at odds with our simple and common heuristic of the hippocampus in memory, it supports the findings of non-human primate studies showing that memory depends on broader medial and lateral TL regions.

Diffusion tractography for awake craniotomy: accuracy and factors affecting specificity.

INTRODUCTION: Despite evidence of correspondence with intraoperative stimulation, there remains limited data on MRI diffusion tractography (DT)'s sensitivity to predict morbidity after neurosurgical oncology treatment. Our aims were: (1) evaluate DT against subcortical stimulation mapping and performance changes during and after awake neurosurgery; (2) evaluate utility of early post-operative DT to predict recovery from post-surgical deficits. METHODS: We retrospectively reviewed our first 100 awake neurosurgery procedures using DT- neuronavigation. Intra-operative stimulation and performance outcomes were assessed to classify DT predictions for sensitivity and specificity calculations. Post-operative DT data, available in 51 patients, were inspected for tract damage. RESULTS: 91 adult brain tumor patients (mean 49.2 years, 43 women) underwent 100 awake surgeries with subcortical stimulation between 2014 and 2019. Sensitivity and specificity of pre-operative DT predictions were 92.2% and 69.2%, varying among tracts. Post-operative deficits occurred after 41 procedures (39%), but were prolonged (> 3 months) in only 4 patients (4%). Post-operative DT in general confirmed surgical preservation of tracts. Post-operative DT anticipated complete recovery in a patient with supplementary motor area syndrome, and indicated infarct-related damage to corticospinal fibers associated with delayed, partial recovery in a second patient. CONCLUSIONS: Pre-operative DT provided very accurate predictions of the spatial location of tracts in relation to a tumor. As expected, however, the presence of a tract did not inform its functional status, resulting in variable DT specificity among individual tracts. While prolonged deficits were rare, DT in the immediate post-operative period offered additional potential to monitor neurological deficits and anticipate recovery potential.

Tracking longitudinal language network reorganisation using functional MRI connectivity fingerprints.

Large individual differences in how brain networks respond to treatment hinder efforts to personalise treatment in neurological conditions. We used a brain network fingerprinting approach to longitudinally track re-organisation of complementary phonological and semantic language networks in 19 patients before and after brain-tumour surgery. Patient task fingerprints were individually compared to normal networks established in 17 healthy controls. Additionally, pre- and post-operative patient fingerprints were directly compared to assess longitudinal network adaptations. We found that task networks remained stable over time in healthy controls, whereas treatment induced reorganisation in 47.4% of patient fluency networks and 15.8% of semantic networks. How networks adapted after surgery was highly unique; a subset of patients (10%) showed 'normalisation' while others (21%) developed newly atypical networks after treatment. The strongest predictor of adaptation of the fluency network was the presence of clinically reported language symptoms. Our findings indicate a tight coupling between processes disrupting performance and neural network adaptation, the patterns of which appear to be both task- and individually-unique. We propose that connectivity fingerprinting offers potential as a clinical marker to track adaptation of specific functional networks across treatment interventions over time.

Presurgical Localization of the Primary Sensorimotor Cortex in Gliomas : When is Resting State FMRI Beneficial and Sufficient?

PURPOSE: Functional magnetic resonance imaging (fMRI) has an established role in neurosurgical planning; however, ambiguity surrounds the comparative value of resting and task-based fMRI relative to anatomical localization of the sensorimotor cortex. This study was carried out to determine: 1) how often fMRI adds to prediction of motor risks beyond expert neuroradiological review, 2) success rates of presurgical resting and task-based sensorimotor mapping, and 3) the impact of accelerated resting fMRI acquisitions on network detectability. METHODS: Data were collected at 2 centers from 71 patients with a primary brain tumor (31 women; mean age 41.9 ± 13.9 years) and 14 healthy individuals (6 women; mean age 37.9 ± 12.7 years). Preoperative 3T MRI included anatomical scans and resting fMRI using unaccelerated (TR = 3.5 s), intermediate (TR = 1.56 s) or high temporal resolution (TR = 0.72 s) sequences. Task fMRI finger tapping data were acquired in 45 patients. Group differences in fMRI reproducibility, spatial overlap and success frequencies were assessed with t­tests and χ2-tests. RESULTS: Radiological review identified the central sulcus in 98.6% (70/71) patients. Task-fMRI succeeded in 100% (45/45). Resting fMRI failed to identify a sensorimotor network in up to 10 patients; it succeeded in 97.9% (47/48) of accelerated fMRIs, compared to only 60.9% (14/23) of unaccelerated fMRIs ([Formula: see text](2) = 17.84, p < 0.001). Of the patients 12 experienced postoperative deterioration, largely predicted by anatomical proximity to the central sulcus. CONCLUSION: The use of fMRI in patients with residual or intact presurgical motor function added value to uncertain anatomical localization in just a single peri-Rolandic glioma case. Resting fMRI showed high correspondence to task localization when acquired with accelerated sequences but offered limited success at standard acquisitions.

Raman spectroscopy to differentiate between fresh tissue samples of glioma and normal brain: a comparison with 5-ALA-induced fluorescence-guided surgery.

OBJECTIVE: Raman spectroscopy is a biophotonic tool that can be used to differentiate between different tissue types. It is nondestructive and no sample preparation is required. The aim of this study was to evaluate the ability of Raman spectroscopy to differentiate between glioma and normal brain when using fresh biopsy samples and, in the case of glioblastomas, to compare the performance of Raman spectroscopy to predict the presence or absence of tumor with that of 5-aminolevulinic acid (5-ALA)-induced fluorescence. METHODS: A principal component analysis (PCA)-fed linear discriminant analysis (LDA) machine learning predictive model was built using Raman spectra, acquired ex vivo, from fresh tissue samples of 62 patients with glioma and 11 glioma-free brain samples from individuals undergoing temporal lobectomy for epilepsy. This model was then used to classify Raman spectra from fresh biopsies from resection cavities after functional guided, supramaximal glioma resection. In cases of glioblastoma, 5-ALA-induced fluorescence at the resection cavity biopsy site was recorded, and this was compared with the Raman spectral model prediction for the presence of tumor. RESULTS: The PCA-LDA predictive model demonstrated 0.96 sensitivity, 0.99 specificity, and 0.99 accuracy for differentiating tumor from normal brain. Twenty-three resection cavity biopsies were taken from 8 patients after supramaximal resection (6 glioblastomas, 2 oligodendrogliomas). Raman spectroscopy showed 1.00 sensitivity, 1.00 specificity, and 1.00 accuracy for predicting tumor versus normal brain in these samples. In the glioblastoma cases, where 5-ALA-induced fluorescence was used, the performance of Raman spectroscopy was significantly better than the predictive value of 5-ALA-induced fluorescence, which showed 0.07 sensitivity, 1.00 specificity, and 0.24 accuracy (p = 0.0009). CONCLUSIONS: Raman spectroscopy can accurately classify fresh tissue samples into tumor versus normal brain and is superior to 5-ALA-induced fluorescence. Raman spectroscopy could become an important intraoperative tool used in conjunction with 5-ALA-induced fluorescence to guide extent of resection in glioma surgery.

The white matter connectome as an individualized biomarker of language impairment in temporal lobe epilepsy.

OBJECTIVE: The distributed white matter network underlying language leads to difficulties in extracting clinically meaningful summaries of neural alterations leading to language impairment. Here we determine the predictive ability of the structural connectome (SC), compared with global measures of white matter tract microstructure and clinical data, to discriminate language impaired patients with temporal lobe epilepsy (TLE) from TLE patients without language impairment. METHODS: T1- and diffusion-MRI, clinical variables (CVs), and neuropsychological measures of naming and verbal fluency were available for 82 TLE patients. Prediction of language impairment was performed using a robust tree-based classifier (XGBoost) for three models: (1) a CV-model which included demographic and epilepsy-related clinical features, (2) an atlas-based tract-model, including four frontotemporal white matter association tracts implicated in language (i.e., the bilateral arcuate fasciculus, inferior frontal occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus), and (3) a SC-model based on diffusion MRI. For the association tracts, mean fractional anisotropy was calculated as a measure of white matter microstructure for each tract using a diffusion tensor atlas (i.e., AtlasTrack). The SC-model used measurement of cortical-cortical connections arising from a temporal lobe subnetwork derived using probabilistic tractography. Dimensionality reduction of the SC was performed with principal components analysis (PCA). Each model was trained on 49 patients from one epilepsy center and tested on 33 patients from a different center (i.e., an independent dataset). Randomization was performed to test the stability of the results. RESULTS: The SC-model yielded a greater area under the curve (AUC; .73) and accuracy (79%) compared to both the tract-model (AUC: .54, p < .001; accuracy: 70%, p < .001) and the CV-model (AUC: .59, p < .001; accuracy: 64%, p < .001). Within the SC-model, lateral temporal connections had the highest importance to model performance, including connections similar to language association tracts such as links between the superior temporal gyrus to pars opercularis. However, in addition to these connections many additional connections that were widely distributed, bilateral and interhemispheric in nature were identified as contributing to SC-model performance. CONCLUSION: The SC revealed a white matter network contributing to language impairment that was widely distributed, bilateral, and lateral temporal in nature. The distributed network underlying language may be why the SC-model has an advantage in identifying sub-components of the complex fiber networks most relevant for aspects of language performance.

Mechanisms and Risk Factors Contributing to Visual Field Deficits following Stereotactic Laser Amygdalohippocampotomy.

Selective laser amygdalohippocampotomy (SLAH) is a minimally invasive surgical treatment for medial temporal lobe epilepsy. Visual field deficits (VFDs) are a significant potential complication. The objective of this study was to determine the relationship between VFDs and potential mechanisms of injury to the optic radiations and lateral geniculate nucleus. We performed a retrospective cross-sectional analysis of 3 patients (5.2%) who developed persistent VFDs after SLAH within our larger series (n = 58), 15 healthy individuals and 10 SLAH patients without visual complications. Diffusion tractography was used to evaluate laser catheter penetration of the optic radiations. Using a complementary approach, we evaluated evidence for focal microstructural tissue damage within the optic radiations and lateral geniculate nucleus. Overablation and potential heat radiation were assessed by quantifying ablation and choroidal fissure CSF volumes as well as energy deposited during SLAH.SLAH treatment parameters did not distinguish VFD patients. Atypically high overlap between the laser catheter and optic radiations was found in 1/3 VFD patients and was accompanied by focal reductions in fractional anisotropy where the catheter entered the lateral occipital white matter. Surprisingly, lateral geniculate tissue diffusivity was abnormal following, but also preceding, SLAH in patients who subsequently developed a VFD (all p = 0.005).In our series, vision-related complications following SLAH, which appear to occur less frequently than following open temporal lobe -surgery, were not directly explained by SLAH treatment parameters. Instead, our data suggest that variations in lateral geniculate structure may influence susceptibility to indirect heat injury from transoccipital SLAH.

Characterising neural plasticity at the single patient level using connectivity fingerprints.

The occurrence of wide-scale neuroplasticity in the injured human brain raises hopes for biomarkers to guide personalised treatment. At the individual level, functional reorganisation has proven challenging to quantify using current techniques that are optimised for population-based analyses. In this cross-sectional study, we acquired functional MRI scans in 44 patients (22 men, 22 women, mean age: 39.4 ±â€¯14 years) with a language-dominant hemisphere brain tumour prior to surgery and 23 healthy volunteers (11 men, 12 women, mean age: 36.3 ±â€¯10.9 years) during performance of a verbal fluency task. We applied a recently developed approach to characterise the normal range of functional connectivity patterns during task performance in healthy controls. Next, we statistically quantified differences from the normal in individual patients and evaluated factors driving these differences. We show that the functional connectivity of brain regions involved in language fluency identifies "fingerprints" of brain plasticity in individual patients, not detected using standard task-evoked analyses. In contrast to healthy controls, patients with a tumour in their language dominant hemisphere showed highly variable fingerprints that uniquely distinguished individuals. Atypical fingerprints were influenced by tumour grade and tumour location relative to the typical fluency-activated network. Our findings show how alterations in brain networks can be visualised and statistically quantified from connectivity fingerprints in individual brains. We propose that connectivity fingerprints offer a statistical metric of individually-specific network organisation through which behaviourally-relevant adaptations could be formally quantified and monitored across individuals, treatments and time.

MRS and DTI evidence of progressive posterior cingulate cortex and corpus callosum injury in the hyper-acute phase after Traumatic Brain Injury.

The posterior cingulate cortex (PCC) and corpus callosum (CC) are susceptible to trauma, but injury often evades detection. PCC Metabolic disruption may predict CC white matter tract injury and the secondary cascade responsible for progression. While the time frame for the secondary cascade remains unclear in humans, the first 24 h (hyper-acute phase) are crucial for life-saving interventions. Objectives: To test whether Magnetic Resonance Imaging (MRI) markers are detectable in the hyper-acute phase and progress after traumatic brain injury (TBI) and whether alterations in these parameters reflect injury severity. Methods: Spectroscopic and diffusion-weighted MRI data were collected in 18 patients with TBI (within 24 h and repeated 7-15 days following injury) and 18 healthy controls (scanned once). Results: Within 24 h of TBI N-acetylaspartate was reduced (F = 11.43, p = 0.002) and choline increased (F = 10.67, p = 0.003), the latter driven by moderate-severe injury (F = 5.54, p = 0.03). Alterations in fractional anisotropy (FA) and axial diffusivity (AD) progressed between the two time-points in the splenium of the CC (p = 0.029 and p = 0.013). Gradual reductions in FA correlated with progressive increases in choline (p = 0.029). Conclusions: Metabolic disruption and structural injury can be detected within hours of trauma. Metabolic and diffusion parameters allow identification of severity and provide evidence of injury progression.

A Noninvasive Comparison Study between Human Gliomas with IDH1 and IDH2 Mutations by MR Spectroscopy.

The oncogenes that are expressed in gliomas reprogram particular pathways of glucose, amino acids, and fatty acid metabolism. Mutations in isocitrate dehydrogenase genes (IDH1/2) in diffuse gliomas are associated with abnormally high levels of 2-hydroxyglutarate (2-HG) levels. The aim of this study was to determine whether metabolic reprogramming associated with IDH mutant gliomas leads to additional ¹H MRS-detectable differences between IDH1 and IDH2 mutations, and to identify metabolites correlated with 2-HG. A total of 21 glioma patients (age= 37 ± 11, 13 males) were recruited for magnetic resonance spectroscopy (MRS) using semi-localization by adiabatic selective refocusing pulse sequence at an ultra-high-field (7T). For 20 patients, the tumor mutation subtype was confirmed by immunohistochemistry and DNA sequencing. LCModel analysis was applied for metabolite quantification. A two-sample t-test was used for metabolite comparisons between IDH1 (n = 15) and IDH2 (n = 5) mutant gliomas. The Pearson correlation coefficients between 2-HG and associated metabolites were calculated. A Bonferroni correction was applied for multiple comparison. IDH2 mutant gliomas have a higher level of 2-HG/tCho (total choline=phosphocholine+glycerylphosphorylcholine) (2.48 ± 1.01vs.0.72 ± 0.38, Pc < 0.001) and myo-Inositol/tCho (2.70 ± 0.90 vs. 1.46 ± 0.51, Pc = 0.011) compared to IDH1 mutation gliomas. Associated metabolites, myo-Inositol and glucose+taurine were correlated with 2-HG levels. These results show the improved characterization of the metabolic pathways in IDH1 and IDH2 gliomas for precision medicine.

Hippocampal Functional Dynamics Are Clinically Implicated in Autoimmune Encephalitis With Faciobrachial Dystonic Seizures.

This is the first study to investigate functional brain activity in patients affected by autoimmune encephalitis with faciobrancial dystonic seizures (FBDS). Multimodal 3T MRI scans, including structural neuroimaging (T1-weighted, diffusion weighted) and functional neuroimaging (scene-encoding task known to activate hippocampal regions), were performed. This case series analysis included eight patients treated for autoimmune encephalitis with FBDS, scanned during the convalescent phase of their condition (median 1.1 years post-onset), and eight healthy volunteers. Compared to controls, 50% of patients showed abnormal hippocampal activity during scene-encoding relative to familiar scene-viewing. Higher peak FBDS frequency was significantly related to lower hippocampal activity during scene-encoding (p = 0.02), though not to markers of hippocampal microstructure (mean diffusivity, p = 0.3) or atrophy (normalized volume, p = 0.4). During scene-encoding, stronger within-medial temporal lobe (MTL) functional connectivity correlated with poorer Addenbrooke's Cognitive Examination-Revised memory score (p = 0.03). These findings suggest that in autoimmune encephalitis, frequent seizures may have a long-term impact on hippocampal activity, beyond that of structural damage. These observations also suggest a potential approach to determine on-going MTL performance in this condition to guide long-term management and future clinical trials.

Cognition based bTBI mechanistic criteria; a tool for preventive and therapeutic innovations.

Blast-induced traumatic brain injury has been associated with neurodegenerative and neuropsychiatric disorders. To date, although damage due to oxidative stress appears to be important, the specific mechanistic causes of such disorders remain elusive. Here, to determine the mechanical variables governing the tissue damage eventually cascading into cognitive deficits, we performed a study on the mechanics of rat brain under blast conditions. To this end, experiments were carried out to analyse and correlate post-injury oxidative stress distribution with cognitive deficits on a live rat exposed to blast. A computational model of the rat head was developed from imaging data and validated against in vivo brain displacement measurements. The blast event was reconstructed in silico to provide mechanistic thresholds that best correlate with cognitive damage at the regional neuronal tissue level, irrespectively of the shape or size of the brain tissue types. This approach was leveraged on a human head model where the prediction of cognitive deficits was shown to correlate with literature findings. The mechanistic insights from this work were finally used to propose a novel protective device design roadmap and potential avenues for therapeutic innovations against blast traumatic brain injury.

Endoscopy in Temporal Lobe Glioma and Metastasis Resection: Is There a Role?

BACKGROUND: Surgical access to the temporal lobe is complex with many eloquent white fiber tracts, requiring careful preoperative surgical planning. Many microsurgical approaches to the temporal lobes are described, each with their own disadvantages. The adoption of the endoscope in neurosurgery has increased the options available when treating these difficult access tumors. We present our experience of a novel, minimally invasive, endoscopic approach to resect temporal lobe tumors. METHODS: All patients undergoing endoscopic temporal lobe tumor resection between December 1, 2011 and December 1, 2017, with a single surgeon, were included. Tumors were resected through a minicraniotomy using a high-definition rigid endoscope with a 0- and 30-degree viewing angle. Bimanual resection was performed using standard microsurgical technique. RESULTS: There were 45 patients (22 men and 23 women) with a mean age of 53 years. There were 23 (51%) glioblastoma multiforme, 11 (24%) metastases, 7 (16%) astrocytoma, 3 (7%) anaplastic astrocytoma, and 1 (2%) World Health Organization grade I glioneuronal tumor. In 82.2% of cases (37/45), >95% resection was achieved and 42.2% (19/45) of patients achieving gross total resection. CONCLUSIONS: The endoscope has a role in temporal lobe intraparenchymal tumor surgery, especially in 3 illustrative scenarios: 1) medial temporal, parahippocampal-gyrus low-grade nonenhancing gliomas, 2) subcortical high-grade glioma and metastases medial to the sagittal stratum, and 3) recurrent gliomas with cystic resection cavity. The endoscope offers a safe and useful adjunct to the surgeons' armamentarium in brain tumor surgery. A minimally invasive approach also reduces surgical morbidity and length of stay.

Metabolite-cycled density-weighted concentric rings k-space trajectory (DW-CRT) enables high-resolution 1 H magnetic resonance spectroscopic imaging at 3-Tesla.

Magnetic resonance spectroscopic imaging (MRSI) is a promising technique in both experimental and clinical settings. However, to date, MRSI has been hampered by prohibitively long acquisition times and artifacts caused by subject motion and hardware-related frequency drift. In the present study, we demonstrate that density weighted concentric ring trajectory (DW-CRT) k-space sampling in combination with semi-LASER excitation and metabolite-cycling enables high-resolution MRSI data to be rapidly acquired at 3 Tesla. Single-slice full-intensity MRSI data (short echo time (TE) semi-LASER TE = 32 ms) were acquired from 6 healthy volunteers with an in-plane resolution of 5 × 5 mm in 13 min 30 sec using this approach. Using LCModel analysis, we found that the acquired spectra allowed for the mapping of total N-acetylaspartate (median Cramer-Rao Lower Bound [CRLB] = 3%), glutamate+glutamine (8%), and glutathione (13%). In addition, we demonstrate potential clinical utility of this technique by optimizing the TE to detect 2-hydroxyglutarate (long TE semi-LASER, TE = 110 ms), to produce relevant high-resolution metabolite maps of grade III IDH-mutant oligodendroglioma in a single patient. This study demonstrates the potential utility of MRSI in the clinical setting at 3 Tesla.

A comparison of 2-hydroxyglutarate detection at 3 and 7 T with long-TE semi-LASER.

Abnormally high levels of the 'oncometabolite' 2-hydroxyglutarate (2-HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. In vivo measurement of 2-HG in patients, using magnetic resonance spectroscopy (MRS), has largely been carried out at 3 T, yet signal overlap continues to pose a challenge for 2-HG detection. To combat this, several groups have proposed MRS methods at ultra-high field (≥7 T) where theoretical increases in signal-to-noise ratio and spectral resolution could improve 2-HG detection. Long echo time (long-TE) semi-localization by adiabatic selective refocusing (semi-LASER) (TE = 110 ms) is a promising method for improved 2-HG detection in vivo at either 3 or 7 T owing to the use of broad-band adiabatic localization. Using previously published semi-LASER methods at 3 and 7 T, this study directly compares the detectability of 2-HG in phantoms and in vivo across nine patients. Cramér-Rao lower bounds (CRLBs) of 2-HG fitting were found to be significantly lower at 7 T (6 ± 2%) relative to 3 T (15 ± 7%) (p = 0.0019), yet were larger at 7 T in an IDH wild-type patient. Although no increase in SNR was detected at 7 T (77 ± 26) relative to 3 T (77 ± 30), the detection of 2-HG was greatly enhanced through an improved spectral profile and increased resolution at 7 T. 7 T had a large effect on pairwise fitting correlations between γ-aminobutyric acid (GABA) and 2-HG (p = 0.004), and resulted in smaller coefficients. The increased sensitivity for 2-HG detection using long-TE acquisition at 7 T may allow for more rapid estimation of 2-HG (within a few spectral averages) together with other associated metabolic markers in glioma.

Hippocampal MRS and subfield volumetry at 7T detects dysfunction not specific to seizure focus.

Ultra high-field 7T MRI offers sensitivity to localize hippocampal pathology in temporal lobe epilepsy (TLE), but has rarely been evaluated in patients with normal-appearing clinical MRI. We applied multimodal 7T MRI to assess if focal subfield atrophy and deviations in brain metabolites characterize epileptic hippocampi. Twelve pre-surgical TLE patients (7 MRI-negative) and age-matched healthy volunteers were scanned at 7T. Hippocampal subfields were manually segmented from 600µm isotropic resolution susceptibility-weighted images. Hippocampal metabolite spectra were acquired to determine absolute concentrations of glutamate, glutamine, myo-inositol, NAA, creatine and choline. We performed case-controls analyses, using permutation testing, to identify abnormalities in hippocampal imaging measures in individual patients, for evaluation against clinical evidence of seizure lateralisation and neuropsychological memory test scores. Volume analyses identified hippocampal subfield atrophy in 9/12 patients (75%), commonly affecting CA3. 7/8 patients had altered metabolite concentrations, most showing reduced glutamine levels (62.5%). However, neither volume nor metabolite deviations consistently lateralized the epileptogenic hippocampus. Rather, lower subiculum volumes and glutamine concentrations correlated with impaired verbal memory performance. Hippocampal subfield and metabolic abnormalities detected at 7T appear to reflect pathophysiological processes beyond epileptogenesis. Despite limited diagnostic contributions, these markers show promise to help elucidate mnemonic processing in TLE.

Early detection of cerebral microbleeds following traumatic brain injury using MRI in the hyper-acute phase.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability in people under 45. Advanced imaging techniques to identify injury and classify severity in the first few hours and days following trauma could improve patient stratification and aid clinical decision making. Traumatic cerebral microbleeds (TCMBs), detectable on magnetic resonance susceptibility weighted imaging (SWI), can be used as markers of long-term clinical outcome. However, the relationship between TCMBs and injury severity in the first few hours after injury, and their natural evolution, is unknown. METHODS: We obtained SWI scans in 10 healthy controls, and 13 patients scanned 3-24h following TBI and again at 7-15days. TCMBs were identified and total volume quantified for every lesion in each scan. RESULTS: TCMBs were present in 6 patients, all with more severe injury classified by GCS. No lesions were identified in patients with an initial GCS of 15. Improvement in GCS in the first 15days following injury was significantly associated with a reduction in microbleed volume over the same time-period. CONCLUSION: MRI is feasible in severely injured patients in the first 24h after trauma. Detection of TCMBs using SWI provides an objective early marker of injury severity following trauma. TCMBs revealed in this time frame, offer the potential to help determine the degree of injury, improving stratification, in order to identify patients who require admission to hospital, transfer to a specialist center, or an extended period of intubation on intensive care.